tbuckley/cabot-search huggingface dataset:
Impact of underrepresented populations on clinical outcomes of chemo-immunotherapy for extensive-stage small cell lung cancer: Real-world prospective cohort study.
Authors: Motohiro Tamiya, Daichi Fujimoto, Hiroaki Akamatsu, Takeshi Morimoto, Akito Hata, Hirotaka Matsumoto, Atsushi Nakamura, Yuko Oya, Hisanori Amimoto, Haruko Daga, Hideki Ikeda, Shinya Sakata, Hidekazu Suzuki, Satoshi Ikeda, Yuhei Harutani, Ryota Hiraoka, Masaaki Yanai, Yoichiro Hamamoto, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2022)

8567 Background: Chemo-immunotherapy is the standard 1st-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). Prospective data about underrepresented populations outside the clinical trial such as elderly or poor risk has not been revealed. Methods: We conducted a 32-hospitals prospective cohort study of consecutive patients with ES-SCLC who received carboplatin and etoposide with atezolizumab as 1st-line therapy between September 2019 and September 2020. The primary outcome was 6-months progression-free survival (PFS) probability of all patients. The secondary outcomes were overall survival (OS), PFS, time to treatment failure, objective response rate, safety, and differences in efficacy and safety depending on whether or not the key eligible study criteria of previous trials are met. Results: In total, 207 patients with ES-SCLC were analyzed. The median age was 72 years, and 64 patients (31%) were elderly (≥75 years). Most patients (89%) had a performance status (PS) of 0 or 1. As a result, 132 (64%) was categorized as eligible patients. The 6-months PFS probability of all patients was 38.8 % (95%CI:32.4-45.7%). Between eligible and ineligible patients, there was significant difference of patients who attained disease control (93% versus 77%, p = 0.002). Median PFS was significantly longer in eligible patients than ineligible patients (5.1 vs. 4.7 months; P =.03, HR 0.72 (95% CI 0.53–0.97)), and median OS was longer in eligible patients than ineligible patients, without any significant difference (15.8 vs. 13.1 months; P =.10, HR 0.73 (95% CI 0.51–1.07)). Survival analysis identified a PS score of 0-1 (HR: 0.60, 95% CI: 0.39-0.97, p = 0.03) as a significant predictor of better PFS, while PS score of 0-1 (HR: 0.51, 95% CI: 0.31-0.89, p = 0.01) and younger patients ( &lt; 75 years) (HR: 0.66, 95% CI: 0.45-0.97, p = 0.03) as significant-good predictor of OS. The rate of severe AEs was higher in ineligible patients than in eligible (39% vs. 27%, respectively; p = 0.07), although the difference was not significant. Older age was significantly associated with severe AEs (p = 0.049). Conclusions: The real-world efficacy of chemo-immunotherapy for ES-SCLC was similar to that of pivotal clinical trials. However, trial-ineligible patients with ES-SCLC had poor treatment outcome and the higher rates of severe adverse events in this prospective cohort study. Our study suggests that positive results among the trial eligible patients may not translate to ineligible patients. Clinical trial information: UMIN000038064.
AI-enabled identification prediction of homologous recombination deficiency (HRD) from histopathology images.
Authors: Gowhar Shafi, Shivamurthy P.M., Anand Ulle, Krithika Srinivasan, Aravindan Vasudevan, Vikas Jadhav, Dr Sujit Joshi, Nirmal Vivek Raut, Jayant Khandare, Mohan Uttarwar, Kenneth Joel Bloom
Journal: Journal of Clinical Oncology (2022)

3019 Background: Homologous recombination deficient (HRD) tumors are highly responsive to platinum-based chemotherapy and poly (ADP-ribose) polymerase inhibitor (PARPi) therapy. Pathogenic BRCA-1 and BRCA-2 (BRCA1/2) alterations are key members of the HR DNA repair pathway but genomic instability status, including loss of heterozygosity, telomeric allelic imbalance and large scale state transitions across the genome are also predictive of HRD. HRD testing is currently performed by next generation sequencing which can take 2-4 weeks for results, has a high failure rate, requires significant tissue and is costly. We developed and tested the ability of an AI enabled platform to predict HRD status from the analysis of whole slide imaging of the diagnostic H&amp;E slide. This platform, iPREDICT-HRD is rapid, precise, and cost effective. Methods: The AI engine was trained on 120 H&amp;E slides that were used to identify tumor prior to manual microdisseection for HRD assessment by NGS. Histopathological features were extracted, followed by feature mapping to predict HRD status based on the results of NGS testing. ResNet AI algorithm was trained to segment, annotate and predict HRD status. 10 lac tiles of 256x256 size at 40x magnification were generated per pathological class. 70% of the data set was used for training and 30% for validation of the AI model. Results: Using single blinded clinical samples, iPREDICT-HRD tool detected HRD + ve samples with 99.3% accuracy with 100% sensitivity and 99% specificity in the test set. Patch-level predictions of HRD status demonstrated intra-tumor heterogeneity within the H&amp;E slides. Visual inspection of the heatmap suggested the presence of patches with high predictive ability of HRD status and this outperformed an average HRD score for slides with heterogeneity. Conclusions: AI-enabled prediction of HRD status can be accurately performed on diagnostic H&amp;E slides potentially yielding results quickly and afforadably, even when limited tissue is available for testing.
Evidence of Sialylation pathways alteration in peripheral blood of Brugada Syndrome patients
Authors: A Tarantino, A Ghiroldi, P Creo, S D'imperio, C Giuseppe, E Micaglio, M Monasky, G Vicedomini, C Pappone, L Anastasia
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): RICERCA CORRENTE, Italian Ministry of Health Background Brugada syndrome (BrS) is a cardiac arrhythmia associated with an increased risk of sudden cardiac death (SCD). BrS is considered a genetic disorder, and the most commonly mutated gene is SCN5A, which encodes the alpha subunit of the voltage-gated cardiac sodium channel (NaV1.5). Mutations of SCN5A generally cause impairment of NaV1.5 function, resulting in alteration of the action potential. However, mutations of SCN5A are responsible for only 30% of BrS cases. Therefore, it is conceivable that other mechanisms such as post-translational modifications (PTMs) could affect NaV1.5 activity. Among others, sialylation may alter ion channel activity by carrying a sugar with a negative charge. Alterations in sialylation have previously been described in several cardiovascular diseases, including myocardial infarction, Chagas disease, and congenital disorders of glycosylation, a family of diseases affecting the heart. For these reasons, the aim was to study alterations in sialylation in BrS patients to get new information about the pathogenesis of BrS. Materials and Methods Peripheral blood mononuclear cells (PBMCs) were collected from BrS patients and healthy controls. To characterize the protein sialylation status of PBMCs, SNA lectin, which is sialic acid-binding proteins, was used by Western blot and flow cytometry. Gene expression of enzymes involved in the biosynthesis, activation, transfer, degradation, and recycling of sialic acid was examined in PBMCs by real-time PCR. Results The extracellular and intracellular sialylation levels of PBMCs differed between BrS patients and controls. In particular, CD3+/CD4+ T cells exhibited a lower significant amount of sialic acid. Moreover, gene expression of enzymes involved in the biosynthesis and activation of sialic acid was downregulated in patients compared to controls. In contrast, the sialyltransferases St3Gal1, St3Gal4, and St6Gal2, enzymes responsible for binding sialic acid to the protein surface, showed significant enzyme-specific differences between BrS patients and controls. Moreover, the levels of sialyltransferases and sialylated proteins are inversely correlated with the epicardial area of the cardiac pathological substrate and with potential duration, two clinical indicators of BrS severity. Discussion These preliminary results demonstrate the involvement of sialylation in BrS syndrome and suggest that impairment of the sialylation process may be associated with the onset and/or manifestation of BrS. In addition, biochemical alteration of cells of the BrS immune system was reported for the first time, supporting the hypothesis that BrS is a systemic disease whose final manifestation is an increased risk of SCD.
Epitheliod hemagioendothelioma (EHE) patient-derived model (PDX): Drug activity assessment and validation of novel biomarkers.
Authors: Silvia Stacchiotti, Valentina Zuco, Anna Maria Frezza, Sandro Pasquali, Monica Tortoreto, Silvia Martini, Marta Barisella, Gianpaolo Dagrada, Paul Huang, Robin Lewis Jones, Paolo G Casali, Hugh Leonard, Alessandro Gronchi, Nadia Zaffaroni
Journal: Journal of Clinical Oncology (2022)

11566 Background: EHE is an ultra-rare sarcoma marked by two specific fusions, WWTR1-CAMTA1 (̃90%) and YAP1-TFE3 (̃10%). The clinical course of EHE ranges from indolent to highly aggressive, often associated with systemic paraneoplastic symptoms. Molecular predictors of clinical outcome are unknown. While surgery is the mainstay of treatment in the localized setting, management of advanced disease is challenging due to the rarity and poor sensitivity to conventional chemotherapy. This hampers the conduct of large prospective clinical trials. We report herein the first available EHE PDX (developed at the Istituto Nazionale Tumori, Milan, Italy) (INT), to assess the activity of old and new anticancer agents in EHE and inform future clinical studies. We also report on the preliminary results of a prospective observational study, ongoing in collaboration with The EHE Rare Cancer Charity (UK) and The EHE Foundation (US) aimed at identifying prognostic factors. Methods: A PDX of EHE in SCID mice was generated at INT from a patient (pt) suffering with the aggressive clinical variant, presenting with systemic symptoms. The PDX fully reproduces the originating clinical tumor in terms of morphology, biology ( WWTR1- CAMTA1 positive), overall transcriptomic profile. 2D (monolayer) and 3D (sferoids) cell cultures were established following PDX disaggregation. We have started assessing the comparative activity of currently available drugs (doxorubicin, sirolimus), while the efficacy of novel agents is undergoing. In parallel, we analyzed the presence of a selection of inflammatory cytokines in prospectively collected blood samples from EHE pts who entered an international observational study and we looked at their presence and modulation in the PDX model. Results: PDX experiments showed almost negligible activity of doxorubicin while sirolimus induced an 80% tumor volume inhibition. Biochemical analysis in tumors explanted from sirolimus-treated mice confirmed the down-regulation of mTOR downstream signaling. Among all cytokines, Growth and Differentiation Factor-15 (GDF-15) was found significantly over-expressed in serum of EHE pts (n = 23), particularly those with the most aggressive clinical variant, compared to healthy subjects (n = 23; p&lt; 0.01). Consistently, EHE PDX and cell culture were found to release in the blood/culture medium GDF-15. Sirolimus was found to down-regulate GDF-15 release in both in vivo and in vitro EHE models. Conclusions: Our preliminary results indicate that this EHE PDX model is suitable i) for comparatively assessing the activity of anticancer drugs, and ii) for identifying and pre-clinically validating novel biomarkers. The role of GDF-15 in EHE progression deserves further investigation.
Radical vs. partial cystectomy for urachal carcinoma: A population-based analysis
Authors: R.S. Flammia, F. Chierigo, C. Würnschimmel, B. Horlemann, B. Hoeh, G. Sorce, Z. Tian, C. Leonardo, D. Tilki, C. Terrone, F. Saad, S.F. Shariat, F. Montorsi, F.K.H. Chun, M. Gallucci, P.I. Karakiewicz
Journal: European Urology (2022)
Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy
Authors: Friederike Schaub, Petra Schiller, Robert Hoerster, Daria Kraus, Frank G. Holz, Rainer Guthoff, Hansjürgen Agostini, Martin S. Spitzer, Peter Wiedemann, Albrecht Lommatzsch, Karl T. Boden, Spyridon Dimopoulos, Sebastian Bemme, Svenja Tamm, Mathias Maier, Johann Roider, Philip Enders, Lebriz Altay, Sascha Fauser, Bernd Kirchhof, Andrea Pfeiffer, Sandra Willms, Susanne Binder, Yannik Le Mer, Hartmut Stützer, Klaus-Dieter Lemmen, Ralph Heimke-Brinck, Tobias Borst, Karl Ulrich Bartz-Schmidt, Josep Callizo, Claudia Dahlke, Philipp Eberwein, Christoph Ehlken, Nicolas Feltgen, Andreea Gamulescu, Faik Gelisken, Matthias Gutfleisch, Arno Haus, Horst Helbig, Manuel Hermann, Kai Januschowski, Claudia Jochmann, Tim Krohne, Wolf Lagrèze, Clemens Lange, Chris Lohmann, Marc Andrej Macek, David Märker, Christian Mayer, Petra Meier, Philipp Müther, Philipp Prahs, Konstantine Purtskhvanidze, Matus Rehak, Friederike Schaub, Tina Schick, Steffen Schmitz-Valckenberg, Maximilian Schultheiß, Christos Skevas, Andreas Stahl, Peter Szurman, Jan Darius Unterlauft, Martin Hellmich, Katrin Kuhr
Journal: Ophthalmology (2022)
Association between metastatic pancreatic cancer and environmental quality index.
Authors: Muhammet Ozer, Suleyman Yasin Goksu, Jude Khatib, Salwan Al Mutar, Todd Anthony Aguilera, Herbert Zeh, Shaalan Shaalan Beg, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2022)

e16232 Background: Pancreatic cancer ranks as the 3 rd leading cause of cancer mortality. Overall more than 50% of patients have metastatic disease at diagnosis. In this study, we evaluated the association between the national level Environmental Quality Index (EQI) and metastatic pancreatic cancer in the US. Methods: Adult patients with pancreatic cancer in the SEER database from 2010-2016 were included in this study. The unknown stage was excluded. Patients were categorized into two groups: metastatic vs. non-metastatic disease. EQI provides county-level environmental quality data from 2005-2010 and presents five domains (built, sociodemographic, air, water, land). EQI was categorized into quintiles, with the 5 th quantile representing a poorer environmental quality. We used the multivariable logistic regression analysis to assess the association between EQI quintiles and metastatic pancreatic cancer adjusting by age, gender, and race (White, Black, and Others). In addition, the SEER*Stat was used to evaluate the age-adjusted incidence rate, and the correlation coefficient between EQI domains and incidence rate was calculated. Results: A total of 75,461 pancreatic cancer patients were included; 55% had metastatic disease. In the adjusted multivariable analysis, metastatic pancreatic cancer was associated with poor built EQI (OR 1.06 [1.01-1.11]). Among metastatic pancreatic cancer patients, poor overall EQI was strongly associated with age &gt; 50 years (OR 1.06 [1.01-1.11]) and Black race (OR 1.29 [1.10-1.51]). Lower built EQI domain was associated with &gt; 50 (OR 1.07 [1.02-1.12]) and White race (OR 1.07 [1.02-1.12]). The incidence rate of metastatic pancreatic cancer was positively correlated with total EQI (rho = 0.02, p &lt; 0.001), sociodemographic EQI (rho = 0.23, p &lt; 0.001), land EQI (rho = 0.14, p &lt; 0.001), and air EQI (rho = 0.34, p &lt; 0.001). Conclusions: Using population-based environmental data, we found built EQI to be associated with metastatic pancreatic cancer. Among metastatic pancreatic cancer patients, total environmental quality was associated with older age at diagnosis and the Black race, while built EQI domain was associated with older age at diagnosis and the White race. Environmental quality was positively correlated with the incidence rate of metastatic pancreatic cancer.
Psychological symptoms and quality of life in Chinese early-stage breast cancer patients throughout chemotherapy.
Authors: Bo Lan, Dan Lv, Min Yang, Xiaoying Sun, Li Zhang, Fei Ma
Journal: Journal of Clinical Oncology (2022)

e24145 Background: Breast cancer survivors with psychological problems have lower quality of life (QOL) and higher mortality than those without. It is important to monitor and manage their psychological status. The aim of this study was to examine the incidence and dynamic changes of anxiety/depression during postoperative adjuvant chemotherapy in Chinese breast cancer patients and to clarify the factors associated with anxiety/depression, the importance of family support, and the impact of anxiety/depression on QOL. Methods: In a prospective observational single-centre cohort study with early-stage breast cancer patients (n = 290), d epression and anxiety severity, QOL and social support were measured before chemotherapy, after 2 cycles of chemotherapy, and after the entire course of chemotherapy using the Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) and Chinese version of the Social Support Rating Scale (SSRS), respectively. Canonical correlations were applied to identify correlates between anxiety/depression and demographic and clinical variables. Paired t tests were used to analyse dynamic changes in QOL. Relationships between anxiety/depression and QOL were analysed using two-way repeated measures analysis of covariance (RMANCOVA). Results: Throughout the entire course of chemotherapy, the incidences of anxiety and depression were 35.2% and 44.1%, respectively. 31.4% of the patients had an increased risk for an anxiety disorder before chemotherapy, which decreased to 29.0% after 2 cycles of chemotherapy and slightly increased to 29.3% after completion of chemotherapy. 20.0% of patients had an increased risk of depression before chemotherapy, which shifted to 25.2% and 24.8% after 2 cycles and the entire course of chemotherapy, respectively. Through multivariable analysis, age (p = 0.042), surgical method (p = 0.009), social support (p = 0.001) and breast cancer family history (p = 0.045) were significantly associated with depression. No variables were significantly associated with anxiety. Patients with higher HADS depression/anxiety scores had lower FACT-B scores during chemotherapy (p &lt; 0.001). Conclusions: We observed dynamic changes in depression, anxiety and QOL throughout adjuvant chemotherapy and the associated factors of depression and anxiety. These findings provide guidance for psychological monitoring and support during postoperative chemotherapy of breast cancer patients. Clinical trial information: NCT05055375. [Table: see text]
Disease-free and overall survival outcomes for localized RCC patients by disease stage.
Authors: Naomi B. Haas, Rituparna Bhattacharya, Adesuwa S. Ogbomo, Kentaro Imai, Santosh Gautam, Jackie Rogerio, Rebekah Yu, Jatin Chhabra, Murali Sundaram
Journal: Journal of Clinical Oncology (2022)

e16526 Background: Real world evidence (RWE) on patient outcomes among early-stage non-metastatic renal cell carcinoma (RCC) patients (pts) of different risk groups are limited. This RWE study evaluated disease free survival (DFS) and overall survival (OS) patterns and risk of OS among pts with non-metastatic RCC in the US. Methods: This retrospective analysis identified pts, age ≥18 years, with non-metastatic RCC diagnosis between 01/01/2012-12/31/2015, and surgical treatment for RCC prior to metastatic diagnosis. Pts were identified from the ConcertAI Oncology Dataset which draws electronic medical records from 100 community oncology clinics in the US and followed until 08/19/2021. Pts were stratified into intermediate (int)-high (pT2N0 high grade, pT3N0) or high risk (pT4N0, pTanyN1) RCC. Time to event outcomes (DFS, OS) were examined using Kaplan-Meier methods, and association of recurrence and 5yr OS was examined using Cox proportional hazard model, controlling for baseline and clinical characteristics. DFS was defined as time from initial nephrectomy to first recurrence or death, whichever occurred first. OS was defined as time from initial nephrectomy to death. Results: The study included 274 pts (87% int-high risk, N = 239; 13% high risk, N = 35). Overall, pts were 63.5 yrs (median age), 66% male, 78% White, and 73% had clear cell RCC. Median follow-up was 49.5 months (mths). 54% int-high and 69% high risk pts had recurrence. As seen in the table, median DFS ranged from 14.6-64.8 mths and 5yr DFS rates ranged from 10-61% across risk groups. Median OS was 83.4 mths for int-high and 78.4 mths for high risk pts; 5yr OS rate was 69% for int-high and 58% for high risk. Compared to patients without recurrence, pts with recurrence had shorter median OS (93.8 vs 69.6 mths) and lower 5yr OS rate (85% vs 57%). In pts with recurrence, 5yr OS rate was similar between int-high and high risk groups (58% and 57%). Pts with recurrence were 2.4 times (HR = 2.4; 95% CI = 1.5, 3.9) more likely to die 5 yrs post initial nephrectomy compared to pts without recurrence. Conclusions: This study confirms findings from our previous research with SEER data that pts with recurrence had an increased risk of death, compared to pts without. The DFS and OS rates observed in this RWE study are supportive of DFS and OS rates observed in the placebo arm of the KEYNOTE-564 trial. Additionally, poor DFS rates were observed within subgroups of int-high risk pts. The study results indicate the high real-world unmet need in post-nephrectomy int-high or high risk localized RCC pts, highlight the need for effective adjuvant treatments, and inform the design of future interventional trials in non-metastatic RCC pts.[Table: see text]
Ventricular Assist Device May Be Faulty
Authors: Howard D. Larkin
Journal: JAMA (2022)

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